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dc.contributor.authorVider, Jelenaen_US
dc.date.accessioned2012-04-11en_US
dc.date.accessioned2012-07-12T23:14:43Z
dc.date.accessioned2017-03-01T22:51:50Z
dc.date.available2017-03-01T22:51:50Z
dc.date.issued2003en_US
dc.date.modified2012-07-12T23:14:43Z
dc.identifier.issn0022-1767en_US
dc.identifier.urihttp://hdl.handle.net/10072/45827
dc.description.abstractEvasion of host immune responses is well documented for viruses and may also occur during tumor immunosurveillance. The mechanisms involve alterations in MHC class I expression, Ag processing and presentation, chemokine and cytokine production, and lymphocyte receptor expression. Epithelial tumors overexpress MHC class I chain-related (MIC) molecules, which are ligands for the activating receptor NKG2D on NK and T cells. We report that NK cells from patients with colorectal cancer lack expression of activating NKG2D and chemokine CXCR1 receptors, both of which are internalized. Serum levels of soluble MIC (sMIC) are elevated and are responsible for down-modulation of NKG2D and CXCR1. In contrast, high serum levels of CXC ligands, IL-8, and epithelial-neutrophil-activating peptide (ENA-78) do not down-modulate CXCR1. In vitro, internalization of NKG2D and CXCR1 occurs within 4 and 24 h, respectively, of incubating normal NK cells with sMIC-containing serum. Furthermore, natural cytotoxicity receptor NKp44 and chemokine receptor CCR7 are also down-modulated in IL-2-activated NK cells cocultured in MIC-containing serum-an effect secondary to the down-modulation of NKG2D and not directly caused by physical association with sMIC. The patients' NK cells up-regulate expression of NKG2D, NKp44, CXCR1, and CCR7 when cultured in normal serum or anti-MIC Ab-treated autologous serum. NKG2D(+) but not NKG2D(-) NK cells are tumoricidal in vitro, and in vivo they selectively traffic to the xenografted carcinoma, form immunological synapse with tumor cells, and significantly retard tumor growth in the SCID mice. These results suggest that circulating sMIC in the cancer patients deactivates NK immunity by down-modulating important activating and chemokine receptors.en_US
dc.description.peerreviewedYesen_US
dc.description.publicationstatusYesen_US
dc.publisherAmerican Association of Immunologistsen_US
dc.publisher.placeUSAen_US
dc.publisher.urihttp://www.jimmunol.org/content/171/12/6891en_US
dc.relation.ispartofpagefrom6891en_US
dc.relation.ispartofpageto6899en_US
dc.relation.ispartofissue12en_US
dc.relation.ispartofjournalJournal of Immunologyen_US
dc.relation.ispartofvolume171en_US
dc.subject.fieldofresearchCancer Therapy (excl Chemotherapy and Radiation Therapy)en_US
dc.subject.fieldofresearchcode111204en_US
dc.titleEvasion from NK cell immunity by MHC class I chain-related molecules expressing colon adenocarcinoma.en_US
dc.typeJournal article
dc.type.descriptionJournal Articles (Refereed Article)en_US
dc.type.codec1xen_US
gro.facultyGriffith Health Facultyen_US
gro.rights.copyrightSelf-archiving of the author-manuscript version is not yet supported by this journal. Please refer to the journal link for access to the definitive, published version or contact the author[s] for more information.en_US
gro.date.issued2003
gro.hasfulltextNo Full Text


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